VIROLOGICAL AND IMMUNOLOGICAL ANALYSIS OF A TRIPLE COMBINATION PILOT-STUDY WITH LOVIRIDE, LAMIVUDINE AND ZIDOVUDINE IN HIV-1-INFECTED PATIENTS

Objective: To compare two antiretroviral regimens, loviride plus lamiv udine (3TC) plus zidovudine (ZDV) (triple combination) and loviride pl us ZDV (double combination) in terms of pharmacokinetic interactions, tolerability, safety, and immunological and virological efficacy. Stud y design: An open, case-controlled, pharmacokinetic and 24-week contin uous treatment pilot study. Patients: Twenty p24 antigen-positive pati ents, 10 per treatment group, were matched according to p24 antigenaem ia less or more than 100 pg, CD4 count less or more than 150x10(6)/1, and gender. Eight out of 10 cases and seven out of 10 Controls had rec eived previous antiretroviral therapy. Results: No clinically relevant pharmacokinetic interactions were observed. Both treatment combinatio ns were well tolerated. Median absolute and percentage CD4 count incre ases above baseline were more pronounced in the triple combination arm than in the double combination arm. Median p24-antigen and plasma vir aemia level decreases below baseline were more pronounced in the tripl e combination arm. The M(184)I/V mutation was detected in all plasma s amples of triple combination patients examined at week 12. Mutations c onferring resistance to loviride and ZDV were found in a significant s ubset of patients in both treatment arms. Conclusions: Both combinatio n regimens have an excellent safety/tolerability profile, but a higher level of in vivo efficacy is achieved by the triple combination, desp ite genotypic changes conferring resistance to one or all of these age nts. The conclusions drawn are limited by small population size and th e heterogenous pretreatment history. However, they support the validit y of and strongly encourage a rationally designed multidrug combinatio n approach to HIV therapy.